pharm-antimicrobials[1]

8/2/2019 Pharm-Antimicrobials[1]

1/17

Antimicrobials:

Antibiotics:

Classes:

Penicillins Cephalosporins Macrolides Aminoglycosides Lincomycins

Tetracyclines Chloramphenicol Fluoroquinolones Sulfonamides


2/17

1. Penicillinscillin suffix

Sub-Classes Individual Drugs Side Effects Microbes Active

Against

Other:

MOA: Bactericidal

Bactericidal: Weaken cellwall which causes cell wallto take up water & burst

(bactericidal) through

activation of autolysins and

inhibition of

transpeptidases.

Only effective whenundergoing active growth.

Not for prophylactic use

Narrow Spectrum

penicillins:

penicillinasesensitive

Penicillin G

Penicillin V

Diarrhea 1-10% have allergic rnx 5-10% will have cross sensitivityw/ cephalosporins and

carbapenems

Streptococcus,

anaerobes.

Distributed best with inflammation (due to

increased blood flow)

Broad spectrum

penicillins:

aminopenicillins

Ampicillin

Amoxicillin

Diarrhea (mostly with AmpicillinPO)

1-10% have allergic rnx 5-10% will have cross sensitivity

w/ cephalosporins and

carbapenems

E. coli

Modes of Resistance:

1. Inability to reach target

2. Inactivation of Penicillin by

bacterial enzymes (Beta-

Lactamases)

Beta-Lactamases cleavebeta-lactam rings. If

specific to PCNs, they are

called pencillinases

(PCNase).

Narrow Sprectrum

penicillins:penicillinase

resistant

Methicillin (no

longer available)

Nafcillin

Oxacillin

Dicloxacillin




carbapenems

Staphylococcus

aureus& epidermis

Methicillin is no longer available due to

MRSA (Methicillin Resistant Staph.)- useVancomycin instead.

Gram Negative producePCNase in small amounts

and secrete them into the

periplasmis space.

Gram-positive producePSNase in large amounts

and export it into the

surrounding medium.

MRSA is resistant toPenicillins because they

have a beta-lactam ring

(like Cephalosporins) which

Extended Spectrum

penicillins:

(antipseudomonal

PCNs)

P. aeruginosa

(main fxn,

aminoglycoside is

usually added to

regimen but do NOT

mix b/c can inactive

aminoglycoside).

Ticarcillin &

Ticarcillin/

clavulanate

Piperacillin &

Piperacillin/

Tazobactam

(usually giving with

aminoglycoside)




carbapenems

E. coli

Pseudomanas

aeruginosa

Ticarcillin:

-Usually administer in high doses in

combination with aminoglycosides.

-Has a disodium salt so can have Na+

overload so be careful in pts with congestive

heart failure (CHF)

-Also interferes with platelet function so

may promote bleeding.


3/17

is the major cause of MRSA

resistance.

Penicillin combo w/

-lactamase inhibitor

Broad:

Ampicillin/

sublactam

Amoxicillin/

clavulanic acid

Extended:

Ticarcillin/clavulanic

acid

Piperacillin/

tazobactam

-By giving as combination extends

antimicrobial spectrum

-Adding clavulanic acid tends to

increase the potential for diarrhea,

especially in children

NOT CEPHALOSPORINS OR CARBAPENEM DUE TO CROSS TOLERENCE POSSIBILITY Na+ overloading with Carbenicillin & Ticarcillin- HTN, CHF Never mix penicillins and aminoglycosides MRSA is resistant to Penicillins due to their beta-lactam ring..


4/17

2. Cephalosporins

ceph, cef prefix

Sub-Classes Individual Drugs Routes/Distrobuti

on

Side Effects Microbes Active

Against

MOA: Bactericidal

Very similar to Penicillins(because molecular structuresare very similar).

Bactericidal: Weaken cell wallwhich causes cell wall to take

up water & burst

(bactericidal) through

activation of autolysins and

inhibition of transpeptidases.

Works best during activegrowth

Modes of Resistance: Beta-Lactamases cleave beta-

lactam rings. If specific to

Cephalosporins, th ey are

called cephalosporinases.

PBPs produced by Methicillin-resistant staphylococci make

it resistant to cephalosporins

(does not treat MRSA).

MRSA is resistant toCephalosporins because they

have a beta-lactam ring (like

Penicillins) which is the major

cause of MRSA resistance.

First generation

Destroyed by cephalosporinase( lactamase)

Good for UTI, Bronchitis, RTI, Skininfections

Used most often b/c1. Inexpensive2. Often as effective as

newer narrower spectrum

drugs

Cephalexin CSF distribution: Poor 5-10% will have

cross sensitivity w/

penicillins

Gram + high

Gram- low

Second Generation

Less sensitive to cephalosporinase( lactamase)

Good for upper RTI

Cefoxitin Cefuroxime is the only

one that can be given

PO and IV

CSF distribution: Poor

5-10% will have


penicillins

Gram + moderate

Gram higher

Third Generation

Highly resistant to cephalosporinase( lactamase)

most effective against meningitis(but not first choice to tx)

Cefotaxime CSF distribution: Good 5-10% will havecross sensitivity w/

penicillins

Gram + lowGram High, some

activity against

Pseudomonis

Aeruginosa

Fourth Generation

Highly resistant to cephalosporinase( lactamase)

Cefepime

(Only 4th

generation)

CSF distribution: Good 5-10% will have


penicillins

Gram + High

Gram highest

Extensive againt

Pseudomonis

Aeruginosia


5/17

3.Carbapenems

w/ Cephalosporins

enem sufix

Individual

Drugs

Uses Microbes Active Against

MOA: Bactericidal

Able to cross gram wallModes of Resistance:

For Pseudomona Aeruginosa, use in combo(Cephalosporins/Carbapenems) to prevent

resistance

Most resistant to lactamases

Meropenem -Bacterial meningitis > 3 y/o,

-Complicated intraabdominal infection

in children and adults.

Pseudomonas Aeruginosa, MRSA

Ertapenem UTI Little action again Pseudomonas Aeruginosa,

pneumococcia, or MRSA.

Imipenem/

Cilastatin


6/17

4.Vancomycin Routes/Distrobution

Uses Side Effects Microbes Active Against Doses

MOA: Bactericidal

-Binds to molecules

that are precursors tocell wall synthesis.

-No lactame ring!

-Usually given in

the hospital

setting.

-Slow IV over 60

minutes or more

(radpid infusion

may cause Red

Man Syndrome)

-PO only for

infection of small

intestine

-Intrathecal IV for

menigile infection

(so it can get toCSF stat)

Only for very seriousinfections

P. colitis (casued by C.difficile)- but try

metronidazole/flagyl first

(it is cheaper, but NO

ETOH within 72 hrs of

use!!!).

MRSA MRS epidermidis Patients that have serious

infection but are allergic

to Penicillins or

cephalosporins (for staph

or strep endocarditis)

Red man syndrome (caused byfast IV- go slow!)

Permenate Ototoxicity (ringing inears) w/ >30mcg/ml

Thrombophlebitis- change site,dilute

Nephrotoxicity

-Active against Gram + only

S. aures, S. epidermidis, C. dificile (but

use metronidazole/flagyl 1st

)

-Monitor serum drug

levels

-Check peak andtrough levels (peak

levels of 30-40 mcg/ml

are acceptable)


7/17

5.Tetracyclines

Cycline suffix

Sub-classesBroad spectrum

antibiotic.

Route Uses Microbes

Active against

Side Effects Other

MOA: Bacteriostatic

-Inhibit protein synthesis.

-2nd

line of defense.

Inhibit bacterial protein

synthesis which

suppresses cell growth

and replication but are

only bacteriostatic.

Short Acting

Low lipid

solubility:

Tetracycline

Oxytetracycline

Give PO if

cannot giveIV.

IM rarely.

Reduced

by food.

Acne

PUD- in combo

with

metrodiazole/flagyl

Periodontal

disease

(Doxycycline

inhibits

collagenase an

enzyme that

destroys

connective tissue -

in the gums).

H. pylori,

Bacillus anthracis

Chelation due to + ions which negatively affects absorption.

Therefore, avoid calcium (milk), iron, zinc, aluminum andmagnesium antacids, and vitamins.

Teeth: Binds to Ca+ in developing teeth causing brown/yellow

discoloration. If used in pregnancy will not affect permanent teeth.

Avoid in children under 8 y/o when tooth enamel is being formed.

Stunts long bone growth and is reversible when treatment stops.

Diarrhea could be indication of suprainfection (C. difficle, aka

antibiotic-associated pseudomembranous colitis). If this occurs,

give metronidazole/flagyl first, then vancomycin.

Fungi in mouth, pharynx, vagina, and bowel (Candida albicans)- stoptetracycline.

Hepatotoxicity

Renaltoxicity

Phototoxicity (use sunscreen when on this medicine)

Short and

intermediate-acting should NOT

be given to

patients with

renal failure. You

can give long

acting (doxycycline

and minocycline).

Intermediate

Acting

Demeclocycline

Widely distributed,

CSF penetration is

poor so do not

treat meingealinfection.

Readily crosses the

placenta and

enters fetal

circulation. Try to

avoid in pregnant

women.

Long Acting High

lipid solubility:

Doxycycline

Minocycline

Food does

not affect

absorption


8/17

6.Macrolides Individualdrugs

Uses Routes/

Distribution

Side Effects Microbes Active

Against

Elimination

MOA: Usually

bacteristatic but can

be bactericidal.

Huge molecules.

Broad Spectrum that

inhibit bacterial

protein synthesis.

Similar to PCN and

cephalosporins.

Erythromycin

Clarithomycin

Azithromycin

Dirithromycin

Troleandomycin

Therapeutic Uses.

If Allergic to PCN

DOC in Bordetella pertussis

(Whooping cough), acute

diphtheria

Mycobacterium avium complex

(MAC) infections in pts. Withadvance HIV infection

Take on empty

stomach.

Metallic taste.

P. colitis (C.

difficile).

H. pylori

Mycobacterium avium

(MAC) in HIV infection.

Hepatically metabolized

by P 450. Interaction w/

Theophylline, warfarin,

carbamazepine

7.Lincosamide IndividualDrug

Routes/

Distribution

Uses Side Effects

MOA: Bacterialstatic,

may be bacterialcidal.

Clindamycin NOT affected

by food.

Only indicated for certain anaerobic infection

located outside the CNS.

Good alternative to Penicillin.

Can promote severe antibiotic-associated

pseudomembranous colitis (C. difficile) can be fatal. If

pt. is experiencing diarrhea stop tx immediately. Candevelop during 1st

week of treatment but may develop

4-6 weeks after treatment ends.


9/17

8.Chloramphinicol

(Chloromycetin)

Uses/Spectrum Routes/

Distribution

Nursing

Management

dosing

Side effect Elimination

MOA: Mostly Bacteriostatic Broad spectrum antibiotic.

Limited to serious & life

threatening infectionsbecause of its ability to cause

fatal aplastic anemia

Neiseria Meningitis.

PO- chloramphenicol

base (active

immediately)

IV_ chloramphenicol

siccinate prodrug (has

to be

converted/metabolized

before it is effective).

Take on anempty

stomach.

Reduce dose inpatients with

liver

dysfunction

NARROW THERAPEUTIC INDEX Monitor serum levels (peak and trough) especially in

neonates, infants and children use.

Dose-dependent bone marrow suppression and graysyndrome in infants.

Aplastic anemia (not dose dependent) develops weeks-months after treatment stops.

Hepaticallymetabolized by

P 450.Interaction w/

Theophylline,

warfarin,

carbamazepine.

9.Aminoglycosides Individualdrugs

Uses/

Spectrum

Routes/

Distribution

Drug interactions Side Effects Elimination

MOA: Bacteriocidal

Has to have O2 towork

Mode of Resistance:

More than 20 differentaminoglycoside-

inactivating enzymes

Amikacin is Leastsusceptible to inactivation

by bacterial enzymes (So

use as a last resort drug)

Gentamicin

Tobramycin

Amikacin

Kanamicin

Neomycin

Streptomycin

E. coli

Pseudomonas

Aeruginosa

Dose must be individualized.

Once daily dosing: just monitor

trough levels.

Bid or tid dosing monitor peak and

trough.

Almost always given in the hospital

setting.

Must be administered parenterally

to treat systemic infections

because it is not absorbed in the

GI tract (no PO form!)

Penicillins: Used together

sometimes. In high

concentrations can inactivate

aminoglycosides. NEVER mix

Penicillin and Aminoglycosides

in the same IV solution (mixing

increases bacterial killcapability of aminoglycosides).

Limited use due

to ototoxicity

and

nephrotoxicity.

Eliminated by the

kidneys (be careful if

patient is renal

impaired).


10/17

10.Sulfonamides Uses Spectrum Side/Adverse EffectsMOA:

Inhibits the sequentialenzymes in the

tetrahydrofolic acid

pathway which preventsbacterial replication.

Folic acid is required for

synthesis of DNA, RNA &

protein

UTI (most caused

by E. coli)

MRSA

E. coli

Kkernicterus (in newborns displaces bilirubin) do not give to infants < 2 y/o, pregnant women or if

breast feeding

Renal damage (crystal formation) take with a lot of water

Photosensitivity

10b.Sulfamethoxazole/Trimethoprim Uses/Spectrum

MOA: Bactericidal/bacterialstatic, broad spectrum

Decrease in folate-spinabifida

Gram negative Enterobacteriaceae (NOT P. aeurginosa).

UTI.

Chronic carinii pneumonia in AIDS patients.

Widely distributed, including into the CSF but not for meningitis.


11/17

11.Fluoroquinolones

Floxacin suffix

Uses/spectrum Side Effects

MOA: Very Broad spectrum

Bacterialcidal

Individual Drugs: Ciprofloxacin,

gatifloxacin, levofloxacin,

moxifloxcin, Lomefloxacin,

norfloxacin, sparfloxacin,

gemifloxacin & ofloxacin

Clostridium difficile is resistant. CSF penetration is low (not

meningitis).

UTI

Ciprofloxacin can be used forchildren.

Systemic use causes tendon injury so do NOT use in children< 18

Possible tendon rupture Photosensitivity Candida infections

Drug interactions

-Chelation due to + ions which negatively affects absorption. Therefore, avoid calcium

(milk), iron, zinc, aluminum and magnesium antacids, and vitamins.

Hepatically metabolized by P 450. Interaction w/ Theophylline, warfarin, carbamazepine.


12/17

Antifungals:1.Amphotericin B Uses Routes/Distributoin Side/Adverse Effects

Broad Spectrum

Antifungal

DOC for systemic

fungi infections

but highly toxic

Only used for

progressive & fatal

infections

Resistance in rare.

Not easily absorbed by CSF

All doses given IV infusion over 2-4 hours, qd to qodfor 2-4 months.

Detected in tissues up to a year after withdrawal.

Infusion reaction.

*Nephrotoxicity*: in almost all pts. (dose dependantover tx period) usually reversible unless dose is over 4

grams. Check kidney function every 3-4 days.

Stays in system for years

Other Antifungals: Azole suffix Fluconazole Itraconazole Ketoconazole Miconazole Clotrimazole Voriconazole

2. Azole antifungals Side/Adverse Effects Elimination

Alternative to Amphotericin B (safer and PO, IV) Take with food and cola to inc absorption

Do not use for superficial fungal infections

IV or PO: Cardio suppressiondecrease ventricular ejection fraction

but return to normal in 12 hours after

dosing

Liver injury (Check LFTs when takingPO)

Inhibits liver metabolizing enzymes

Inhibits CYP450 enzyme.

Hepatically metabolized by P 450. Interaction w/ Theophylline,

warfarin, carbamazepine.

3.Flucytosine Side/Adverse Effects

Reserved to serious infections of Candida & Cryptococcusneoformans

Excreted by the kidneys Hepatotoxicity Absolutely monitor renal function.


13/17

Antivirals:

Ganciclovir Uses Side/Adverse Effects

Cytomegalovirus (CMV): Occurs person to person (body fluids)

Can remain dormant in cells for life but becomes a problem in the immunocomp pts (HIV, cancer etc) ***Teratogenic***

Interferon Alfa Uses

Hep B

Classes of HIV Antivirals:NRTI (nucleoside reverse transcriptase inhibitor)

NNRTI (non-nucleoside reverse transcriptase inhibitors)

Protease Inhibitors

Fusion Inhibitor


14/17

Other:

Specific: Drug used to treat: Subclasses: Other:

E. Coli Broad Spectrum Penicillins Amplicillin

AmoxicillinExtended Spectrum Penicillins

(Antipseudomonal)

Ticarcillin

Ticarcillin/clavulanate

Piperacillin

Piperacillin/tazobactam

Aminoglycosides GentamicinTobramycin

Amikacin

Kanamicin

Neomycin

Streptomycin

Sulfonamides(Sulfamaethoxazole/Trimethoprim)

Fluoroquinolones

C. difficile.

Causes

Pseudomembranous

Colitis

Vancomycin 1st

treatment

Metronidazole/flagyl,

then Vancomycin.

C. difficile is resistant to

Fluoroquinolones

(Flaxacin suffix)

TetracyclinesTetracycline, oxytetracycline,

demeclorycline, doxycycline, minocycline

Lincosamide Clindamycin

Staphylococcus Aureus

MRSA

Narrow Spectrum Pencillins

(Penicillinase resistant)

Nafcillin

Oxacillin

Dicloxacillin

NOT Methicillin

Carbepenems w/ Cephalosporins Meropenem

Vancomycin

Sulfonamides


15/17

H. Pylori

PUD

Tetracylines Tetracycline, oxtetracycline,demeclorycline, doxycyline, minocycline

Macrolides ErythromycinClarithomycin

AzithromycinDirithromycin

Troleandomycin

Neiseria Meningitis Cephalosporins 3rd

generation Cefotaxime NOTSulfamethoxazole/Trimethoprin,

Fluoroquinolones (Floxacin

suffix)

Carbapenems/cephalosporins Meropenem Okay for >3 y/o

Chloramphinicol (Chloromycetin)

Pseudomonas

Aeruginosa

Extended Spectrum Penicillins TicarcillinTicarcillin/clavulanate

Piperacillin

Piperacillin/tazobactam

NOT

Sufonamides

Sulfamethoxazole/trimethoprim

Cephalosporins 4th

generation: Cefepine

3rd

generation: Cefotaxime

Carbapenems w/ cephalosporins Meropenem


Amikacin

Kanamicin

Neomycin

Streptomycin

AIDS Macrolides (Mycobacterium aviumcomplex) MAC

Sulfanethoxazole/Trimethoprim

(Chronic carinii pneumonia)

P450

Interact w/


Azithromycin


16/17

Theophylline, warfarin,

Carbamazepine

Dirithromycin

Troleandomycin

Chloramphinicol -(Chloromycetin)

Fluoroquinolones Floxacin suffix

Chelation Fluoroquinolones Floxacin suffix

Tetracyclines Cycline suffix

Allergic to Penicillins /

Cephalosporins

Vancomycin (serious infection)


Azithromycin

Dirithromycin

Troleandomycin

Lincosamde (clindamycin)

Phototoxicity Tetracyclines Cycline suffix

Sulfonamides

Fluoroquinolones Floxacin suffix

Ototoxicity Vancomycin


Amikacin

Kanamicin

NeomycinStreptomycin

Nephrotoxicity Vancomycin

Tetracyclines (short and

intermediate)

Tetracycline

Oxytetracycline

Demeclocycline


Amikacin

Kanamicin


17/17

Neomycin

Streptomycin

NSAIDS

Aspirin

CyclosporinePolymyxins

Amphotericin B

pharm-antimicrobials[1]

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